Rapamycin promotes Schwann cell migration and nerve growth factor secretion

Rapamycin, similar to FKS06, can promote neural regeneration in vitro. We assumed that the mechanisms of action of rapamycin and FK506 in promoting peripheral nerve regeneration were similar. This study compared the effects of different concentrations of raparnycin and FK506 on Sc hwann cells and investigated effects and mechanisms of rapamycin on improving peripheral nerve regeneration. Results demonstrated that the lowest rapamycin concentration （1.53 nmol/L） more significantly promoted Schwann cell migration than the highest FK506 concentration （100μmol/L）. Rapamycin promoted the secretion of nerve growth factors and upregulated growth-associated protein 43 expression in Schwann cells, but did not significantly affect Schwann cell proliferation. Therefore, rapamycin has potential application in peripheral nerve regeneration therapy.

Hyaluronic acid methacrylate/laponite hydrogel loaded with BMP4 and maintaining its bioactivity for scar-free wound healing

Scar-free wound healing is a challenging process due to the excessive deposition of extracellular matrix and collagen.To overcome this issue,hydrogels with superior biochemical and mechanical properties have been used in combination with medicinal compounds as wound dressings.In this study,a novel composite hydrogel consisting of double-crosslinked photocurable hyaluronic acid methacrylate(HAMA)and Laponite(Lap)loaded with bioactive bone morphogenetic protein 4(BMP4)was developed and thoroughly characterized for its properties such as degradation,morphology,porosity,compression,skin adhesion and load release.The effect of the HAMA/Lap/BMP4 hydrogel was evaluated through both in vitro and in vivo experiments.In the in vivo rabbit ear-scar model,the HAMA/Lap/BMP4 hydrogel dressing was found to reduce scar-related expressions ofα-SAM and decrease the ratio of collagenΙ/III in wounded tissue.Additionally,histopathological examination indicated that the HAMA/Lap/BMP4 hydrogel-treated groups exhibited enhanced wound repair and increased levels of collagen maintenance compared to other standard groups,ultimately leading to scarless wound healing.Therefore,this sustained-release photocurable HAMA/Lap/BMP4 hydrogel offers a therapeutic approach for scar-free wound healing.

Promotion of peripheral nerve regeneration and prevention of neuroma formation by PRGD/PDLLA/b-TCP conduit:report of two cases

In the field of nerve repair,one major challenge is the formation of neuroma.However,reports on both the promotion of nerve regeneration and prevention of traumatic neuroma in the clinical settings are rare in the field of nerve repair.One of the reasons could be the insufficiency in the follow-up system.We have conducted 33 cases of nerve repair using PRGD/PDLLA/b-TCP conduit without any sign of adverse reaction,especially no neuroma formation.Among them,we have selected two cases as representatives to report in this article.The first case was a patient with an upper limb nerve wound was bridged by PRGD/PDLLA/b-TCP conduit and a plate fixation was given.After nearly 3-years’follow-up,the examination results demonstrated that nerve regeneration effect was very good.When the reoperation was performed to remove the steel plate we observed a uniform structure of the regenerated nerve without the formation of neuroma,and to our delight,the implanted conduit was completely degraded 23 months after the implantation.The second case had an obsolete nerve injury with neuroma formation.After removal of the neuroma,the nerve was bridged by PRGD/PDLLA/b-TCP conduit.Follow-up examinations showed that the structure and functional recovery were improved gradually in the 10-month follow-up;no end-enlargement and any other abnormal reaction associated with the characteristic of neuroma were found.Based on our 33-case studies,we have concluded that PRGD/PDLLA/b-TCP nerve conduit could both promote nerve regeneration and prevent neuroma formation;therefore,it is a good alternative for peripheral nerve repair.

Conductive ionic liquid/chitosan hydrogels for neuronal cell differentiation

To regulate cell behaviors and promote nerve function recovery,three-dimensional(3D)conductive hydrogel can transmit intercellular electrical signals,and effectively provide the cell survival environment.However,produc-ing hydrogels with simultaneous high conductivity,favorable biocompatibility,and tissue-matching properties remains a challenge for spinal cord injury(SCI)treatment.Here,a conductive,multifunctional,and biocompati-ble VPImBF4 ionic liquid(IL)with photosensitive chitosan-based hydrogel(pCM@IL)is developed.The pCM@IL hydrogel exhibits a 3D microporous structure that could maintain cell viability and improve cell growth.Elas-tic modulus,conductivity,and biodegradability of the pCM@IL hydrogels are investigated with tissue-matching mechanical properties.The pCM@IL conductive hydrogels synergistically enhance neuronal cell proliferation and promote neuronal cells differentiation via upregulates synapse gene(Tubulin𝛽3,GAP43,Synaptophysin)expression.Furthermore,in vivo studies of the pCM@IL conductive hydrogels as implants demonstrate low-inflammation and neovascularize promotion and appropriate biodegradable properties.The developed pCM@IL conductive hydrogel is a promising therapeutic scaffold biomaterial for SCI repair.